MEIS2 suppresses breast cancer development by downregulating IL10.

BACKGROUND: Breast cancer (BC) is the most commonly diagnosed female cancer. Homeobox protein MEIS2, a key transcription factor, is involved in the regulation of many developmental and cellular processes. However, the role of MEIS2 in the development of breast cancer is still unclear. AIMS: We aimed to examine the role of myeloid ecotropic insertion site (MEIS2) in breast cancer and the association of MEIS2 with breast cancer clinical stages and pathological grades. We revealed the underlying mechanism by which MEIS2 affected breast cancer cell growth and tumor development. METHODS AND RESULTS: Using human BC cell lines, clinical samples and animal xenograft model, we reveal that MEIS2 functions as a tumor suppressor in breast cancer. The expression of MEIS2 is inversely correlated with BC clinical stages and pathological grades. MEIS2 knockdown (MEIS2-KD) promotes while MEIS2 overexpression suppresses breast cancer cell proliferation and tumor development in vitro and in animal xenograft models, respectively. To determine the biological function of MEIS2, we screen the expression of a group of MEIS2 potential targeting genes in stable-established cell lines. Results show that the knockdown of MEIS2 in breast cancer cells up-regulates the IL10 expression, but MEIS2 overexpression opposed the effect on IL10 expression. Furthermore, the suppressive role of MEIS2 in breast cancer cell proliferation is associated with the IL10 expression and myeloid cells infiltration. CONCLUSION: Our study demonstrates that the tumor suppressor of MEIS2 in breast cancer progression is partially via down regulating the expression of IL10 and promoting myeloid cells infiltration. Targeting MEIS2 would be a potentially therapeutic avenue for BC.

Triple-Negative Breast Cancer Intrinsic FTSJ1 Favors Tumor Progression and Attenuates CD8+ T Cell Infiltration.

FtsJ RNA 2'-O-methyltransferase 1 (FTSJ1) is a member of the methyltransferase superfamily and is involved in the processing and modification of ribosomal RNA. We herein demonstrate that FTSJ1 favors TNBC progression. The knockdown of FTSJ1 inhibits TNBC cell proliferation and development, induces apoptosis of cancer cells, and increases the sensitivity of TNBC cells to T-cell-mediated cytotoxicity. Furthermore, the high expression of FTSJ1 in TNBC attenuates CD8+T cell infiltration in the tumor microenvironment (TME) correlated with poorer prognosis for clinical TNBC patients. In this study, we establish that FTSJ1 acts as a tumor promotor, is involved in cancer immune evasion, and may serve as a potential immunotherapy target in TNBC.

DDX5 Functions as a Tumor Suppressor in Tongue Cancer.

DEAD-box polypeptide 5 (DDX5), a DEAD-box RNA helicase, is a multifunctional protein that plays important roles in many physiological and pathological processes. Contrary to its documented oncogenic role in a wide array of cancers, we herein demonstrate that DDX5 serves as a tumor suppressor in tongue cancer. The high expression of DDX5 is correlated with better prognosis for clinical tongue cancer patients. DDX5 downregulates the genes associated with tongue cancer progression. The knockdown of DDX5 promotes, while the overexpression of DDX5 inhibits, tongue cancer proliferation, development, and cisplatin resistance. Furthermore, the expression of DDX5 in tongue cancer is associated with immune cell infiltration in the tumor microenvironment. Specifically, the expression of DDX5 is associated with the reduced infiltration of M2 macrophages and increased infiltration of T cell clusters, which may contribute to anticancer effects in the tumor microenvironment. In this study, we establish DDX5 as a valuable prognostic biomarker and an important tumor suppressor in tongue cancer.

PRPF19 promotes tongue cancer growth and chemoradiotherapy resistance.

Pre-mRNA processing factor 19 (PRPF19) is a multifaceted protein and participates in DNA damage response and pre-mRNA processing. The role of PRPF19 in cancer is unclear. Here, we report that the expression of PRPF19 in human tongue cancer is associated with unfavorable prognosis. Overexpression of PRPF19 promotes while knockdown of PRPF19 inhibits tongue cancer cell migration, proliferation, and tumor growth. Overexpression of PRPF19 increases the resistance of tongue cancer cells to radiation and cisplatin treatment. Furthermore, PRPF19 regulates the expression of solute carrier family 40 member 1 (SLC40A1) and mono-ADP ribosylhydrolase 2 (MACROD2), knockdown of SLC40A1 or MACROD2 decreases the sensitivity of tongue cancer cells to radiation and cisplatin treatment. Thus, our results establish a key role of PRPF19 in tongue cancer growth and chemoradiotherapy resistance, targeting PRPF19 would be an effective therapeutic strategy for tongue cancer, especially for those resistant to chemoradiotherapy.

Comparison of Dosimetric Gains Provided by Intensity-Modulated Radiotherapy, Volume-Modulated Arc Therapy, and Helical Tomotherapy for High-Grade Glioma.

PURPOSE: Because of the poor prognosis for high-grade glioma (HGG) patients, it is important to increase the dose of the tumor to improve the efficacy while minimizing the dose of organs at risk (OARs). Thus, we evaluated the potential dosimetric gains of helical tomotherapy (HT) versus intensity-modulated radiotherapy (IMRT) or volume-modulated arc therapy (VMAT) for high-grade glioma (HGG). METHODS: A total of 42 HGG patients were retrospectively selected who had undergone helical tomotherapy; then, IMRT and VMAT plans were generated and optimized for comparison after contouring crucial neuronal structures for neurogenesis and neurocognitive function. IMRT and VMAT were optimized with the Eclipse treatment planning system (TPS) (Version 11.0.31) and HT using TomoTherapy Hi-Art Software (Version 2.0.7) (Accuray, Madison, WI, USA). All three techniques were optimized for simultaneously delivering 60 Gy to planning target volume (PTV) 1 and 50-54 Gy to PTV2. We also analyzed the homogeneity index (HI) and conformity index (CI) of PTVs and organ at risk (OAR) sparing. RESULTS: There was no significant difference in the PTV coverage among IMRT, VMAT, or HT. As for the HI, HT plans (PTV1 HI: 0.09 ± 0.03, PTV2 HI: 0.17 ± 0.05) had the best homogeneity when compared to IMRT plans (PTV1 HI: 0.10 ± 0.04, PTV2 HI: 0.18 ± 0.04) and VMAT plans (PTV1 HI: 0.11 ± 0.03, PTV2 HI: 0.20 ± 0.03). The CI value of HT (PTV1 CI: 0.98 ± 0.03, PTV2: 0.98 ± 0.05) was closest to the optimal value. Except for the IMRT and VMAT groups, there were statistically significant differences between the other two groups of the CI values in both PTV1 and PTV2. The other comparison values were statistically significant except for the optic nerve, and VMAT had the best sparing of the optic chiasm. The mean and max doses of OARs declined significantly in HT. CONCLUSIONS: For high-grade glioma patients, HT had superior outcomes in terms of PTV coverage and OAR sparing as compared with IMRT/VMAT.

Dosimetric comparisons of craniospinal axis irradiation using helical tomotherapy, volume-modulated arc therapy and intensity-modulated radiotherapy for medulloblastoma.

BACKGROUND: To evaluate the potential dosimetric gains of helical tomotherapy (HT) versus intensity-modulated radiotherapy (IMRT) and volume-modulated arc therapy (VMAT) for craniospinal axis irradiation (CSI) of medulloblastoma. METHODS: A total of 36 treatment plans were calculated retrospectively for 12 patients with medulloblastoma receiving CSI using HT with TomoTherapy Hi-Art Software (Version 2.0.7) (Accuray, Madison, WI, USA). For each case, the other two different delivery techniques were re-planned with IMRT/VMAT optimized with Eclipse treatment planning system (TPS) (Version 11.0.31). Homogeneity index (HI) and conformity index (CI) of the planning target volume (PTV) and organs at risk (OARs) sparing were analyzed. Differences in plans were evaluated using paired-samples t-test for various dosimetric parameters. RESULTS: HT yielded the highest CI in all PTV coverage including PTV of gross tumor volume (PGTV) (HT: 0.7163; VMAT: 0.6688; IMRT: 0.6096), PTVbrain (HT: 0.8490; VMAT: 0.8384; IMRT: 0.7815) and PTVspine (HT: 0.5904; VMAT: 0.5862; IMRT: 0.5797). Meanwhile, HT yielded better HI in PGTV (HT: 0.0543; VMAT: 0.0759; IMRT: 0.0736), PTVbrain (HT: 0.5525; VMAT: 0.5619; IMRT: 0.5554) and PTVspine (HT: 0.0700; VMAT: 0.0782; IMRT: 0.0877). As for OARs, HT demonstrated marked superiority in critical organs including maximal/mean doses of brainstem PRV, optical chiasm and optic nerves. CONCLUSIONS: For CSI of medulloblastoma, HT offers superior outcomes in terms of PTV conformity, PTV homogeneity and critical OAR sparing as compared with IMRT/VMAT.